Kidney Stones EDITING FILE. Biochemistry Team 437 "الل ھ م لا س ھ ل إ لا ما ج ع ل ت ھ س ھ لا وأن ت ت ج ع ل الح ز ن إذ ا ش ي ت س ھ لا " Renal block

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1 "الل ھ م لا س ھ ل إ لا ما ج ع ل ت ھ س ھ لا وأن ت ت ج ع ل الح ز ن إذ ا ش ي ت س ھ لا " Kidney Stones Biochemistry Team 437 Color index: Doctors slides Doctor s notes Extra information Highlights Renal block EDITING FILE

2 Objectives: By the end of this lecture, the students will be able to: Discuss the general physiological and pathological factors that favor kidney stones formation List the types of kidney stones, their chemical constituents and characteristics Identify the etiological causes of each type of kidney stone Discuss the diagnosis, treatment and prevention of kidney stones 2

3 Overview: Introduction Conditions causing kidney stone formation Types of kidney stones: Calcium salts Uric acid Mg ammonium PO 4 Cystine Other (xanthine, etc.) Laboratory investigations 3

4 Introduction: When a molecule is normally present in the soluble form, but its concentration is too much to the point where it can no longer be solubilized, it precipitates. when these precipitations crystalize and become big, they make kidney stones. What are kidney stones? Renal calculi (kidney stones) are formed in renal tubules, ureter or bladder. Composed of metabolic products present in glomerular filtrate. urea, creatinine, electrolytes These products are in high concentration¹ near² or above maximum solubility³. Causes of kidney stone formation: High conc. of metabolic products in glomerular filtrate. Changes in urine ph. normal is between [ ] Urinary stagnation. Deficiency of stone-forming inhibitors in urine. ¹ If the amount of the solute increase, or the amount of water decreases, the concentration of the solute becomes very high therefore creating stones ² if the conc. Is above maximum solubility, it will precipitate directly. If it was near maximum solubility, any stagnation or change in ph will make it precipitate. ³ maximum solubility is the maximum amount of solute the solvent can solubilize, for example,if we keep adding salt (sodium) to a glass of water. The water will reach a limit which cannot accept any more salt and it accumulates at the bottom of the glass. 4

5 Causes of kidney stone formation High conc. of metabolic products in glomerular filtrate is due to: Changes in urine ph due to: Urinary stagnation is due to: Deficiency of stone-forming inhibitors: Low urinary volume (with normal renal function) due to restricted fluid intake. Increased fluid loss from the body.¹ Increased excretion of metabolic products forming stones. High plasma volume (high filtrate level). ² Low tubular reabsorption from filtrate. Bacterial infection. Dietary,metabolic acidosis/alkalosis Precipitation of salts at different ph: A.persistently.acidic urine.promotes.uric acid precipitation. PH Below 5.5 A persistently alkaline PH above 8 urine (due to upper urinary tract infection) promotes Mg Ammonium Phosphate crystals (Struvite stones). Obstruction.of.urinary flow. These substances are present normally in the urine to inhibit stone formation by different mechanisms.² a deficiency in them will lead to stone formation. ¹Majority of stones are calcium stones ² citrate binds to calcium and affects its solubility, and glycoproteins prevents the crystals from attaching to a certain place in the tubules to form stones Citrate, pyrophosphate, glycoproteins inhibit growth of calcium¹ phosphate and calcium oxalate crystals. In type I renal tubular acidosis³, hypocitraturia⁴ leads to renal stones. ¹ Sweating, diuretics, type 2 diabetes ² because it affects the ability of the tubules to reabsorb metabolic products. The bacteria will release an enzyme called urease that converts urea to ammonia and alkalizes the urine. ³Tubular acidosis: Not enough excretion of H+ ions ⁴hypocitraturia is less citrate in the urine 5

6 Types of kidney stones 1) Calcium¹ : Oxalate or Phosphate (Most common form of stones). 2) Magnesium ammonium phosphate (H 4 MgNO 4 P) Forms Struvite stones. 3) Uric acid/urate 4) Cystine Is the least common type of stones 5) Other types of uncommon stones include those induced by drugs or Xanthine We will discuss each stone now in the next slides. ¹ Salt stones are formed mostly in which type of urine? Alkaline urine. Because 80% of the stones are Ca++ stones and calcium stones are formed in alkaline urine 6

7 Calcium Salt Stones 80% of kidney stones contain calcium (mostly ca-oxalates, ca-po4) The type of salt depends on : Urine ph Availability of oxalate General appearance: White, hard, radio-opaque¹ Calcium oxalate: present in ureter (small) Calcium PO4 : staghorn in renal pelvis (large) ¹ Radiopaque: appears on X-ray Calcium oxalate stones 7

8 Causes of Calcium Salt Stones 1) Hypercalciuria: 2) Hyperoxaluria³: 3) Primary hyperoxaluria: Increased urinary calcium excretion Men: > 7.5 mmols/day Women > 6.2 mmols/day Tip: you don't have to memorize these numbers A) Due to hypercalcemia¹ (most often due to primary* hyperparathyroidism²) B) Sometimes, ca+ stones are found with no hypercalcemia A) Causes the formation of calcium oxalates without hypercalciuria B) Diet rich in oxalates Nuts, tomatoes, spinach, fries, potato chips C) Increased oxalate absorption in fat malabsorption⁴ ¹ caused by: Increase intestinal absorption Decrease in kidney reabsorption Bone resorption Hyperparathyroidism A) Due to inborn errors B) Urinary oxalate excretion: > 400 µmol/24 Hours ² Parathyroid hormone is released when calcium is decreased in the body, it works on both the kidneys and the bones. In the bones: increase resorption release of calcium In the kidneys: increase the reabsorption of calcium but not enough to prevent stones *primary: idiopathic ³Oxalate binds to calcium and makes stones, even if the calcium level is not high ⁴ undigested fat in the intestine - when the fat is not absorbed e.g. due to surgery- oxalate absorption will increase, so there will be an increase in oxalate in the blood which will be excreted into the urine, causing increase of oxalate in the urine 8

9 Treatment of Calcium Salt Stones Treatment of primary causes such as infection, hypercalcemia, hyperoxaluria Oxalate-restricted diet Increased fluid intake (if no glomerular failure) Acidification of urine (by dietary changes eating meats) Calcium salt stones are formed in alkaline urine 9

10 Uric acid stones About 8% of renal stones contain uric acid May be associated with hyperuricemia (with or without gout) Form in acidic urine ¹ General appearance : Small, friable², yellowish May form staghorn (if big and mixed) Radiolucent (plain x-rays cannot detect) Visualized by ultrasound or i.v. pyelogram ¹meat consumption makes the urine more acidic while fruit consumption alkalizes the urine ²crumbles easily 10

11 Uric acid stones Treatment: Treatment of cause of hyperuricemia. Purine-restricted diet Because it s the origin of Uric acid Alkalinization of urine (by dietary changes:eating Vegetables) Increased fluid intake Eating Vegetable and fruits > Alkalization of urine > For acid stones Eating Meat > Acidification of urine > For Alkaline stones An option To treat any kidney stone is to affect the urines acidity or alkalinity this can be achieved by dietary changes. (Meats and alcohols are acidic, vegetables and fruits are alkaline.) in this type of kidney stone we would increase acidic foods to correct the alkalinity of the urine by acidifying it. Summary 11

12 Mg ammonium PO 4 stones (Also called struvite kidney stones) Infection is prime factor to struvite stones. Bacterial infection leads to increase in urease activity Urease will metabolize urea into ammonia, which will change the PH to alkaline which leads to Mg stone formations. About 10% of all renal stones contain Mg amm. PO 4 Commonly associated with staghorn calculi 75% of staghorn stones are of struvite type Associated with chronic urinary tract infection. Microorganisms (such as from Proteus genus) that has urease activity that metabolize urea into ammonia Causing urine ph to become alkaline leading to stone formation 12

13 Mg ammonium PO 4 stones Treatment: Treatment of infection Urine acidification Increased fluid intake In some cases, it may require complete stone removal (percutaneous nephrolithotomy) Summary Q1: A patient has staghorn stones with no UTI, what is the most likely type of stone? A. Calcium phosphate Q2: A patient has a staghorn shaped stone and a UTI, what is the most likely type of stone? A. Struvite stone 13

14 1- A rare type of kidney stone Cystine stones Eating Vegetable > Alkalization of urine > For acid stones Eating Meat > Acidification of urine > For Alkaline stones Characteristics Cystine is a dipeptide that is less soluble. Cystine stones are caused by an inherited disease that inhibits cystine absorption Treatment 2- Due to homozygous cystinuria 3- Form in acidic urine 4- Soluble in alkaline urine 5- Faint radio-opaque 1- Increased fluid intake 2- Alkalinization of urine (by dietary changes) 3- Penicillamine (binds to cysteine to form a compound more soluble than cystine) 14

15 Laboratory investigations of kidney stones If stones has formed and removed: either surgically or normally Chemical analysis of the stones will help us in 2 things 1) Identify the cause 2) Advise the patient to prevent it from happening again and to stop future recurrence a patient that makes a stone is very likely to make more stones, so prevention is important If stones had NOT yet formed: Investigation may help to contribute in knowing CAUSES or factors that may help form the stone: Serum calcium, uric acid, PTH ( parathyroid hormone ) analysis Urinalysis Volume, calcium, oxalate, and cystine levels Urine ph > 8 suggest UTI Mg ammonium phosphate Struvite stones Urinary tract imaging : CT, ultrasound, and I.V Pyelogram I.V Pyelogram 15

16 Summary of types of kidney stone From Team

17 Summary 17

18 MCQs: 1- What is the cause of kidney stone formation in case of bacterial infection? A) Urine stagnation B) High metabolic conc. C) Change in urine PH D) Deficiency in stone forming inhibitors 2- Most common type of kidney stones is? A) Phosphate B) Calcium C) Magnesium D) Uric acid 3- A patient came to you with severe flank pain and haematuria you suspected kidney stones a plan x ray of the kidneys showed nothing you asked for ultrasound and you find small stones in the kidney, after extraction of the stones they appeared to be small friable and yellowish. What is the type of stone? A) Uric acid stone B) Calcium salt stone C) Mg ammonium PO 4 stones D) Glucose stones 4- Which of the following types of kidney stones are also called struvite kidney stones? A) Uric acid stone B) Calcium salt stone C) Mg ammonium PO 4 stones D) Glucose stones 5- Calcium oxalate stones are mainly formed in the? A) Renal Pelvis B) Ureter C) Urethra D) Minor calyx 6- Which of the following doesn t inhibit the formation of growth of calcium phosphate and calcium oxalate crystals? A) Citrate B) Pyrophosphate C) Glycoproteins D) G6PD 1- C 2- B 3- A 4- C 5- B 6- D 18

19 SAQ: SAQ/ In treatment of calcium salt stones why do we treat it by the acidification of urine (by dietary changes)? Because Calcium salt stones are formed in alkaline urine, so by the acidification of the urine we stop the formation of the stones. 19

20 Girls team Boys team Team leaders رھف الشنیبر شھد الجبرین لینا الرحمة منیرة المسعد لیلى الص باغ العنود المنصور أرجوانة العقیل ریناد الغریبي رزان الزھراني لیان المانع مشاعل القحطاني شیرین حمادي مجد البراك رھام الحلبي معاذ الحمود طارق العمیم فیصل الطحان محمد الصویغ أنس القحطاني صالح الوكیل عبد الملك الشرھان سعید القحطاني محمد الاصقھ نواف اللویمي معن شكر عبدالرحمن